The biological roles of exercise-induced cytokines: IL-6, IL-8, and IL-15

2007 ◽  
Vol 32 (5) ◽  
pp. 833-839 ◽  
Author(s):  
Anders Rinnov Nielsen ◽  
Bente Klarlund Pedersen
Keyword(s):  
Skeletal Muscle ◽  
Systemic Circulation ◽  
Glucose Disposal ◽  
Acid Oxidation ◽  
Tissue Mass ◽  
Protein Levels ◽  
Exercise Induced ◽  
Net Release

Skeletal muscle fibers express several cytokines, including interleukin (IL)-6, IL-8, and IL-15. Solid evidence exists that muscular IL-6 and IL-8 are regulated by muscle contractions, at both the mRNA and the protein levels. IL-6 increases insulin-stimulated glucose disposal and fatty acid oxidation in humans in vivo. Both IL-6 and IL-8 are released from working skeletal muscle, but because IL-6 contributes to the systemic circulation only a small transient net release of IL-8 is found from working muscle, suggesting that IL-8 may exert its effects locally in the muscle. IL-15 is a recently discovered growth factor, which is highly expressed in skeletal muscle. Interestingly, although IL-15 has been demonstrated as having anabolic effects on skeletal muscle in vitro and in vivo, it seems to play a role in reducing adipose tissue mass, and a role for IL-15 in muscle–fat cross-talk has been hypothesized. In conclusion, muscle-derived cytokines appear to have important roles in metabolism, and exercise plays a role in orchestrating the interplay between cytokines and metabolism.

scholarly journals Prep1 Deficiency Induces Protection from Diabetes and Increased Insulin Sensitivity through a p160-Mediated Mechanism

2008 ◽  
Vol 28 (18) ◽  
pp. 5634-5645 ◽  
Author(s):  
Francesco Oriente ◽  
Luis Cesar Fernandez Diaz ◽  
Claudia Miele ◽  
Salvatore Iovino ◽  
Silvia Mori ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Glucose Uptake ◽  
Normal Glucose Tolerance ◽  
Glucose Disposal ◽  
Protein Levels ◽  
Normal Glucose ◽  
Enhanced Expression ◽  
The Stability

ABSTRACT We have examined glucose homeostasis in mice hypomorphic for the homeotic transcription factor gene Prep1. Prep1-hypomorphic (Prep1 i / i ) mice exhibit an absolute reduction in circulating insulin levels but normal glucose tolerance. In addition, these mice exhibit protection from streptozotocin-induced diabetes and enhanced insulin sensitivity with improved glucose uptake and insulin-dependent glucose disposal by skeletal muscle. This muscle phenotype does not depend on reduced expression of the known Prep1 transcription partner, Pbx1. Instead, in Prep1 i / i muscle, we find normal Pbx1 but reduced levels of the recently identified novel Prep1 interactor p160. Consistent with this reduction, we find a muscle-selective increase in mRNA and protein levels of PGC-1α, accompanied by enhanced expression of the GLUT4 transporter, responsible for insulin-stimulated glucose uptake in muscle. Indeed, using L6 skeletal muscle cells, we induced the opposite effects by overexpressing Prep1 or p160, but not Pbx1. In vivo skeletal muscle delivery of p160 cDNA in Prep1 i / i mice also reverses the molecular phenotype. Finally, we show that Prep1 controls the stability of the p160 protein. We conclude that Prep1 controls insulin sensitivity through the p160-GLUT4 pathway.

Palmitate oxidation rate and action on glycogen synthase in myoblasts from insulin-resistant subjects

2000 ◽  
Vol 279 (3) ◽  
pp. E561-E569 ◽  
Author(s):  
David M. Mott ◽  
Cristen Hoyt ◽  
Rael Caspari ◽  
Karen Stone ◽  
Richard Pratley ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Glycogen Synthase ◽  
Glucose Disposal ◽  
Nonesterified Fatty Acid ◽  
Palmitate Oxidation ◽  
Oxidation Rates ◽  
Glycogen Synthase Activity

Elevated plasma lipid and nonesterified fatty acid concentrations reduce insulin-mediated glucose disposal in skeletal muscle. Cultured myoblasts from 21 subjects were studied for rates of palmitate oxidation and the effect of palmitate on glycogen synthase activity at the end of an 18-h incubation in serum- and glucose-free media. Oxidation rates of 40 μM palmitate in cultured myoblasts correlated with the fasting glucose ( r = 0.71, P = 0.001), log fasting insulin ( r = 0.52, P = 0.03), and insulin-mediated glucose storage rate ( r = −0.50, P = 0.04) of the muscle donors. Myoblast glycogen synthase activity can be regulated by 240 μM palmitate, but the changes are associated with the basal respiratory quotient and not with the insulin resistance of the muscle donor. These results indicate that myoblasts producing elevated palmitate oxidation rates in vitro can be used to identify skeletal muscle abnormalities which are primary contributors to insulin resistance in vivo. Effects of 240 μM palmitate on myoblast glycogen synthase activity appear to be mechanistically different from the relationship between myoblast palmitate oxidation rates and insulin resistance of the muscle donor.

scholarly journals Sepsis and glucocorticoids upregulate p300 and downregulate HDAC6 expression and activity in skeletal muscle

2010 ◽  
Vol 299 (2) ◽  
pp. R509-R520 ◽  
Author(s):  
Nima Alamdari ◽  
Ira J. Smith ◽  
Zaira Aversa ◽  
Per-Olof Hasselgren
Keyword(s):  
Skeletal Muscle ◽  
Histone Deacetylases ◽  
Muscle Wasting ◽  
Trichostatin A ◽  
Histone Acetyl Transferase ◽  
Hdac Activity ◽  
Protein Levels ◽  
Expression And Activity

Muscle wasting during sepsis is in part regulated by glucocorticoids. In recent studies, treatment of cultured muscle cells in vitro with dexamethasone upregulated expression and activity of p300, a histone acetyl transferase (HAT), and reduced expression and activity of the histone deacetylases-3 (HDAC3) and -6, changes that favor hyperacetylation. Here, we tested the hypothesis that sepsis and glucocorticoids regulate p300 and HDAC3 and -6 in skeletal muscle in vivo. Because sepsis-induced metabolic changes are particularly pronounced in white, fast-twitch skeletal muscle, most experiments were performed in extensor digitorum longus muscles. Sepsis in rats upregulated p300 mRNA and protein levels, stimulated HAT activity, and reduced HDAC6 expression and HDAC activity. The sepsis-induced changes in p300 and HDAC expression were prevented by the glucocorticoid receptor antagonist RU38486. Treatment of rats with dexamethasone increased expression of p300 and HAT activity, reduced expression of HDAC3 and -6, and inhibited HDAC activity. Finally, treatment with the HDAC inhibitor trichostatin A resulted in increased muscle proteolysis and expression of the ubiquitin ligase atrogin-1. Taken together, our results suggest for the first time that sepsis-induced muscle wasting may be regulated by glucocorticoid-dependent hyperacetylation caused by increased p300 and reduced HDAC expression and activity. The recent development of pharmacological HDAC activators may provide a novel avenue to prevent and treat muscle wasting in sepsis and other catabolic conditions.

scholarly journals Contribution of IL-6 to the Hsp72, Hsp25, and αβ-crystallin responses to inflammation and exercise training in mouse skeletal and cardiac muscle

2008 ◽  
Vol 105 (6) ◽  
pp. 1830-1836 ◽  
Author(s):  
Kimberly A. Huey ◽  
Benjamin M. Meador
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Cardiac Muscle ◽  
Wheel Running ◽  
Protein Levels ◽  
Cardiac Muscles ◽  
Exercise Induced ◽  
Shock Proteins ◽  
Dependent Mechanism

The heat shock proteins (Hsps) Hsp72, Hsp25, and αβ-crystallin (αβC) may protect tissues during exercise and/or inflammatory insults; however, no studies have investigated whether exercise training increases both basal and inflammation-induced expression of these Hsps in skeletal or cardiac muscle. IL-6 is produced by muscle during both exercise and inflammation and has been shown to modulate Hsp expression. These studies tested the hypothesis that voluntary wheel running (RW) increases basal and inflammation-induced Hsp72, Hsp25, and αβC protein through an IL-6-dependent mechanism. We compared Hsp72, Hsp25, αβC, and IL-6 protein levels 4 h after systemic inflammation induced by lipopolysaccharide (LPS) in skeletal and cardiac muscles of wild-type (IL-6+/+) and IL-6 deficient (IL-6−/−) mice after 2 wk of RW or normal cage activity (Sed). LPS significantly increased skeletal Hsp72 and Hsp25 relative to saline in Sed IL-6+/+, but not IL-6−/− mice. LPS increased Hsp72 relative to saline in Sed IL-6+/+ cardiac muscle. RW increased basal Hsp72, Hsp25, and αβC in skeletal muscle in IL-6+/+ and IL-6−/− mice. However, LPS was not associated with increases in any Hsp in RW IL-6+/+ or IL-6−/− mice. LPS increased IL-6 protein in skeletal muscle and plasma in Sed and RW groups, with a significantly greater response in RW. The major results provide the first in vivo evidence that the absence of IL-6 is associated with reduced skeletal muscle Hsp72 and Hsp25 responses to LPS, but that IL-6 is not required for exercise-induced Hsp upregulation in skeletal or cardiac muscle.

scholarly journals Testosterone Promotes the Proliferation of Chicken Embryonic Myoblasts Via Androgen Receptor Mediated PI3K/Akt Signaling Pathway

2020 ◽  
Vol 21 (3) ◽  
pp. 1152 ◽  
Author(s):  
Dongfeng Li ◽  
Qin Wang ◽  
Kai Shi ◽  
Yinglin Lu ◽  
Debing Yu ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Androgen Receptor ◽  
Muscle Development ◽  
Fiber Formation ◽  
Cross Sectional ◽  
Protein Levels ◽  
Proliferative Effect ◽  
Phosphoinositide 3 Kinase

Testosterone (T) is essential for muscle fiber formation and growth. However, the specific mechanism by which T regulates skeletal muscle development in chicken embryos remains unclear. In this study, the role of T in myoblast proliferation both in vivo and in vitro was investigated. Results showed that the T administration significantly increased the ratio of breast muscle and leg muscle. T induced a significant increase in the cross-sectional area (CSA) and density of myofiber and the ratio of PAX7-positive cells in the skeletal muscle. Exogenous T also induced the upregulation of myogenic regulatory factors (MRFs) and cyclin-dependent kinases (CDK2)/Cyclin D1 (CCND1) and protein levels of androgen receptor (AR), p-Akt and PAX7. Furthermore, T treatment significantly promoted myoblasts cultured in vitro entering a new cell cycle and increased PAX7-positive cells. The mRNA and protein expression of AR and PAX7 were upregulated when treated with T compared to that of the control. The addition of T induced proliferation accompanied by increasing AR level as well as PI3K (Phosphoinositide 3-kinase)/Akt activation. However, T-induced proliferation was attenuated by AR, PI3K, and Akt-specific inhibitors. These data indicated that the pro-proliferative effect of T was regulated though AR in response to the activation of PI3K/Akt signalling pathway.

Increased phenylalanine incorporation in regenerating skeletal muscle grafts

1986 ◽  
Vol 64 (2) ◽  
pp. 199-205 ◽  
Author(s):  
Jessica Schwartz ◽  
Jane Wiesen ◽  
Bruce Carlson ◽  
L. Yamasaki ◽  
M. Moore ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Fibers ◽  
Maximal Increase ◽  
Tissue Mass ◽  
Wet Weight ◽  
Edl Muscle

Skeletal muscle regenerates following grafting, but little is known about protein synthesis and its regulation during regeneration. We determined the sequence of changes in protein synthesis in rat extensor digitorum longus (EDL) muscle by the measurement of phenylalanine (Phe) incorporation into muscle protein at various times after grafting. Compared with control EDL, Phe incorporation in grafts doubled in 1 day, was four- to eight-fold greater from days 2 to 10 after grafting, and then subsided. Tissue mass (wet weight) increased rapidly from days 7 to 20 in EDL grafts. The maximal increase in protein synthesis occurred 7–10 days after grafting, whether or not the nerve was left intact. Autoradiography indicated that incorporated radioactivity was associated with regenerating muscle fibers on day 10. Deficiencies of insulin, pituitary or testicular hormones, or chronic in vivo administration of insulin, growth hormone, testosterone, or tri-iodothyronine did not substantially alter the elevation in incorporation of the Phe into muscle protein 10 days after grafting. The breakdown of EDL protein, measured in vitro simultaneously with protein synthesis, was increased five-fold, and overall protein degradation was elevated six-fold 10 days after grafting. These findings indicate that Phe incorporation is rapidly elevated following grafting of the EDL, and that by days 7–10 reflects synthesis in regenerating muscle fibers. The increase in protein synthesis associated with muscle regeneration at this time appears to be independent of innervation and anabolic hormones.

Evidence for Abnormal Na+/H+ Antiport Activity Detected by Phosphorus Nuclear Magnetic Resonance Spectroscopy in Exercising Skeletal Muscle of Patients with Essential Hypertension

1990 ◽  
Vol 79 (5) ◽  
pp. 491-497 ◽  
Author(s):  
C. R. K. Dudley ◽  
D. J. Taylor ◽  
L. L. Ng ◽  
G. J. Kemp ◽  
P. J. Ratcliffe ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Essential Hypertension ◽  
Resonance Spectroscopy ◽  
Isotonic Exercise ◽  
Muscle Ph ◽  
Acid Load ◽  
Exercise Induced ◽  
Acid Loading

1. Exercise-induced pH changes in skeletal muscle were studied in a group of eight subjects with essential hypertension by using 31P n.m.r. spectroscopy. 2. Leucocyte Na+/H+ antiport activity was measured in vitro in the same subjects using a pH-sensitive fluorescent dye. 3. Resting skeletal muscle pH and unstimulated leucocyte pH values were similar to those in control subjects, but increased Na+/H+ antiport activity was demonstrated in the leucocytes from hypertensive subjects by acid loading in vitro. Decreased skeletal muscle acidification and an increased rate of pH recovery was also demonstrated in vivo in these same patients during an acid load induced by isotonic exercise. 4. These findings suggest that the increased cellular Na+/H+ antiport activity, which has been demonstrated in vitro in essential hypertension, also affects the biochemical response of skeletal muscle to physiological levels of exercise. This strengthens the argument that increased Na+/H+ antiport activity in hypertension is a generalized and physiologically relevant cellular abnormality.

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